We propose to study epithelial renewal in experimental and clinical peptic ulcer disease, during acute and chronic administration of potential ulcerogens, and during malignant transformation of experimental gastric ulcer after exposure to a carcinogen (MNNG). The methods which have been and will be used include light microscopy, light autoradiography, electron microscopy in both rats and humans and, in humans, organ culture of upper gastrointestinal biopsies. In rats, we have already studied epithelial renewal in the stomach and duodenum after exposure to aspirin, steroids, or alcohol. We have also administered the carcinogen, MNNG, to rats which have intact stomachs and to other rats in which experimental ulcers have been formed. Results of these studies to date indicate that aspirin stimulates epithelial renewal in the stomach and steroids depress epithelial renewal in the stomach and possibly also in the duodenum. MNNG causes frank mucosal damage to both gastric and small intestine mucosa and expands the proliferative zone. In humans, we will study epithelial renewal in patients with peptic ulcer disease, before and after healing, in patients with acute gastritis of diverse etiology, and in patients who chronically consume potential ulcerogens such as aspirin, ethanol, or steroids. We have studied only a few patients to date and have no data at this time.